Fragrance compounds

ABSTRACT

Novel compounds having the structure (I) where R and R 1  is each independently hydrogen or an alkyl, alkenyl, cycloalkyl or cycloalkenyl group having from 1 to 5 carbon atoms can have desirable odour properties, typically of a peach, fruity, lactone or nitrile character and find use in perfumes and perfumed products. Fragrance uses of 6-phenylhexan-2-one are also disclosed.

FIELD OF THE INVENTION

This invention concerns novel fragrance compounds and methods of makingthem, and perfumes and perfumed products comprising the novel compounds.

SUMMARY OF THE INVENTION

In one aspect of the present invention provides a compound having thestructure

where R and R¹ is each independently hydrogen or an alkyl, alkenyl,cycloalkyl or cycloalkenyl group having from 1 to 5 carbon atoms.

For brevity and simplicity, such materials will be referred to as “thenitrile”, “the novel nitrile” or “the nitrile of the invention”.

The nitriles of the invention can occur in two different versions,dependent on the position of the double bond, which are referred toherein as version 1 or nitrile 1 and version 2 or nitrile 2, asindicated above. The invention covers each version alone and alsomixtures of the two versions.

The nitriles of the invention can possess fragrance or odour propertieswhich are generally regarded as interesting, pleasant or attractive,typically having peach, fruity, lactone or nitrile odour properties.

The odour properties of the nitriles of the invention mean that anitrile or mixture of nitriles in accordance with the invention may beused as such to impart, strengthen or improve the odour of a widevariety of products, or may be used as a component of a perfume (orfragrance composition) to contribute its odour character to the overallodour of such perfume. For the purposes of this invention a perfume isintended to mean a mixture of fragrance materials, if desired mixed withor dissolved in a suitable solvent or mixed with a solid substrate,which is used to impart a desired odour to the skin and/or product forwhich an agreeable odour is indispensable or desirable. Example of suchproducts are: fabric washing powers, washing liquids, fabric softenersand other fabric care products; detergents and household cleaning,scouring and disinfection products; air fresheners, room sprays andpomanders; soaps, bath and shower gels, shampoos, hair conditioners andother personal cleansing products; cosmetics such as creams, ointments,toilet waters, preshave, aftershave, skin and other lotions, talcumpowers, body deodorants and antiperspirants, etc. Nitriles in accordancewith the invention can show good substantivity to cloth, both wet anddry, and hence have good potential for use in fabric treatment products.

Other fragrance materials which can be advantageously combined with oneor more nitriles according to the invention in a perfume are, forexample, natural products such as extracts, essential oils, absolutes,resinoids, resins, concretes etc., but also synthetic materials such ashydrocarbons, alcohols, aldehydes, ketones, ethers, acids, esters,acetals, ketals, nitriles, etc., including saturated and unsaturatedcompounds, aliphatic, carbocyclic, and heterocyclic compounds.

Such fragrance materials are mentioned, for example, in S. Arctander,Perfume and Flavor Chemicals (Montclair, N.J., 1969), in S. Arctander,Perfume and Flavor Materials of Natural Origin (Elizabeth, N.J., 1960)and in “Flavor and Fragrance Materials—1991”, Allured Publishing Co.Wheaton, Ill. USA.

Examples of fragrance materials which can be used in combination withone or more nitriles according to the invention are: geraniol, geranylacetate, linalol, linalyl acetate, tetrahydrolinalol, citronellol,citronellyl acetate, dihydromyrcenol, dihydromyrcenyl acetate,tetrahydromyrcenol, terpineol, terpinyl acetate, nonpol, nopyl acetate,2-phenyl-ethanol, 2-penylethyl acetate, benzyl alcohol, benzyl acetate,benzyl salicylate, styrallyl acetate, benzyl benzoate, amyl salicylate,dimethylbenzyl-carbinol, trichloromethylphenyl-carbinyl acetate,p-tert-butylcyclohexyl acetate, isononyl acetate, vetiveryl acetate,vetiverol α-hexylcinnamaldehyde, 2-methyl-3-(p-tert-butylpheyl)propanal,2methyl-3-(p-isopropylphenyl)propanal, 2-(p-tert-butylpheyl)-propanal,2,4-dimethyl-cyclohex-3-enyl-carboxaldehyde, tricyclodecenyl acetate,tricyclodecenylpropionate,4-(4-hydroxy-4-methylpentyl)-3-cyclohexenecarboxyaldehyde,4-(4-methyl-3-pentenyl)-3-cyclohexenecarboxaldehyde,4-acetoxy-3-pentyl-tetrahydropyran,3-carboxymethyl-2-pentylcyclopentane, 2-n-heptylcyclopentanone,3-methyl-2-pentyl-2-cyclopentenone, n-decanal, n-dodecanal, 9-decenol-1,phenoxyethyl isobutyrate, phenyl-acetaldehyde dimethylacetal,phenylacetaldehyde diethylacetal, geranyl nitrile, citronellyl nitrile,cedryl acetate, 3-isocamphylcyclohexanol, cedryl methyl ether,isolongifolanone, aubepine nitrile, aubepine, heliotropin, coumarin,eugenol, vanillin, diphenyl oxide, hydroxycitronellal, ionones,methylionones, isomethylionones, irones, cis-3-hexenol and estersthereof, indan musks, tetralin musks, isochroman musks, macrocyclicketones, macrolactone musks, ethylene brassylate.

Solvents which can be used for perfumes which contain a nitrileaccording to the invention are, for example: ethanol, isopropanol,diethyleneglycol monoethyl ether, dipropylene glycol, diethyl phthalate,triethyl citrate, isopropyl myristate, etc.

The quantities in which one or more nitriles according to the inventioncan be used in perfumes or in products to be perfumed may vary withinwide limits and depend, inter alia, on the nature of the product, on thenature and the quantity of the other components of the perfume in whichthe nitrile is used and on the olfactive effect desired. It is thereforeonly possible to specify wide limits, which, however, provide sufficientinformation for the specialist in the art to be able to use a nitrilesaccording to the invention for his specific purpose. In perfumes anamount of 0.01% by weight or more of a nitrile according to theinvention will generally have a clearly perceptible olfactive effect.Preferably the amount is 0.1 to 80% by weight, more preferably at least1%. The amount of the nitrile according to the invention present inproducts will generally be at least 10 ppm by weight, preferably atleast 100 ppm, more preferably at least 1000 ppm. However, levels of upto about 20% by weight may be used in particular cases, depending on theproduct to be perfumed.

The nitriles exist in various isomeric forms. The invention covers eachisomeric form alone, and mixtures of different isomeric forms, and alsothe use in perfumes and perfumed products of separate isomers andmixtures of isomers.

The currently preferred nitriles in accordance with the invention haveR═CH₃ and R¹═H. In this case nitrile 1 has the structure

and is 3-methyl-7-phenyl-2-heptenenitrile; nitrile 2 has the structure

and is 3-methyl-7-phenyl-3-heptenenitrile. Both of these materials existas both E and Z isomers. Both of these preferred nitriles have peach,fruity, lactone, nitrile odour properties. The nitrile aspects of theodour properties also give the materials power and intensity of smell.Both of these materials are very substantive on both wet and dry cloth,and so have good potential for use in fabric treatment products such asfabric detergents.

In a further aspect the invention provides a perfume comprising one ormore nitriles of the invention in an olfactively effective amount.

The invention also covers a perfumed product comprising one or morenitriles of the invention.

Nitriles in accordance with the invention may be synthesised by Aldolcondensation of cinnamaldehyde and a suitable ketone, followed byhydrogenation. A Wadsworth Emmons reaction may be performed on theproduct, to yield a version 1 nitrile. Alternatively, a Knoevenagelcondensation may be performed on the product, to yield a mixture ofversion 1 and version 2 nitriles, which may be used as a mixture orseparated. For example, the preferred nitriles referred to above,3-methyl-7-phenyl-2-heptenenitrile and3-methyl-7-phenyl-3-heptenenitrile, may be readily and cheaplysynthesised by Aldol condensation of cinnamaldehyde with acetone,followed by hydrogenation to yield 6-phenylhexan-2-one. Wadsworth Emmonsreaction of 6-phenylhexan-2-one yields3-methyl-7-phenyl-2-heptenenitrile (as a mixture of E and Z isomers).Alternatively, Knoevenagel condensation of 6-phenylhexan-2-one withcyanoacetic acid yields a mixture of 3-methyl-7-phenyl-2-heptenenitrileand 3-methyl-7-phenyl-3-heptenenitrile (each as a mixture of E and Zisomers). Reaction of the mixture with potassium tert-butoxide yields3-methyl-7-phenyl-2-heptenenitrile.

In a further aspect, the invention thus provides a method of making anitrile in accordance with the invention, comprising

-   i) performing an Aldol condensation of cinnamaldehyde with a ketone;-   ii) hydrogenating the product of step i); and-   iii) performing a Wadsworth Emmons reaction or a Knoevenagel    condensation reaction on the product of step ii).

6-phenylhexan-2-one, which has the following structure:

which is produced as an intermediate in the process referred to above,has jasmine-like odour properties, and so has potential fragrance use asan inexpensive jasmine-type filler material. While this material isknown per se in the literature, the odour properties of the materialhave not previously been disclosed. The present invention thus alsoincludes within its scope fragrance uses of this material.

Thus, the invention also provides a perfume comprising6-phenylhexan-2-one in an olfactively effective amount.

In a further aspect, the invention also covers a perfumed productcomprising 6-phenylhexan-2-one.

The invention, in a further aspect, also covers a process for impartinga jasmine-type odour note to a perfume or perfumed product, comprisingincorporating 6-phenylhexan-2-one into the perfume or product.

The terms perfume and perfumed product as used here have the samemeaning as discussed above, and should be construed accordingly.

The invention will be further described, by way of illustration, in thefollowing Examples.

EXAMPLE 1

This example describes synthesis routes for3-methyl-7-phenyl-2-heptenenitrile (material III in the reaction schemebelow), and a mixture of 3-methyl-7-phenyl-3-heptenenitrile (material IVin the reaction scheme below) with 3-methyl-7-phenyl-2-heptenenitrile,involving production as an intermediate 6-phenylhexan-2-one (material IIin the reaction scheme below).

The synthesis routes are illustrated in the following reaction scheme:

Reaction 1 Aldol Reaction Between Cinamaldehyde and Acetone to Produce ICinamaldehyde 396.0 g, 3.0 mol Acetone 660 ml, 9.0 mol Sodium Hydroxide60.0 g, 1.5 mol Water 6 ltr

The above four ingredients were heated to 70° C. (using an immersioncirculator) and then allowed to cool. A yellow solidprecipitated/crystallised out on cooling. The solid was dissolved by theaddition of ethyl acetate with stirring. The organic solution wasseparated, dried with magnesium sulphate, and concentrated down toapproximately 1200 ml (91% of one component by GC). This solution wasused in the next step without any further purification.

Reaction 2 Hydrogenation of Crude Aldol Product to Yield II Crude Aldolproduct 1200 ml solution from reaction 1 Palladium (5% on carbon) 2 × 5g (Hydrogenated in two portions) Hydrogen

The solution was hydrogenated in two portions in a glass Buchi autoclaveat 4-6 bar. Initially each portion showed an exotherm where thetemperature rose up to 45-50° C. The reaction was monitored by GC andonce complete was filtered through celite and the residual solventremoved by evaporation. The resulting residue was distilled to yield thefollowing two fractions which were both found to be the desired product:

87-88° C. @ 0.1 mmHg, 132.9 g (97.7% by GC)

90-110° C. @ 0.2 mmHg, 277.0 g (97.6% by GC)

¹³C NMR data analysis: (CDCl₃, ref 77.0 ppm) 208.9 (C═O), 142.3 (CQ),128.5 (CH), 128.4 (CH), 125.8 (CH), 43.6 (CH), 35.8 (CH₂), 31.0(CH₂),29.9 (CH₃), 23.5 (CH₂)

Preparation of Target Molecule III

Route 1:

Reaction 3 Wadsworth Emmons Horner Reaction on II 6-Phenylhexan-2-one(II) 133.0 g, 0.76 mol n-BuLi (10M, Aldrich, in THF) 88 ml, 0.88 molTetrahydrofuran (HPLC grade) 1 ltr Diethylcyanomethylphosphonate 141.0g, 0.80 mol

The n-BuLi solution (pyrophoric) was added dropwise to the phosphonatein tetrahydrofuran over a period of 1-2 hrs whilst maintaining thetemperature below 50° C. (this addition is exothermic). The reactionmixture became orange/clear in appearance with a small amount ofcolourless solid also being present. This solution was left overnight.

To this orange solution was then added the ketone 6-phenylhexan-2-oneover a period of about one hour. This addition was mildly exothermicwith the temperature rising to 45° C. over the course of the addition.Once the addition was complete the resulting solution was left to coolovernight. The solvent was removed under reduced pressure and theresidue was poured into water (1 ltr). This was then extracted withdiethyl ether (2×500 ml) and the combined organic fractions were thenwashed with water (500 ml), dried with magnesium sulphate, andevaporated under reduced pressure. The resulting residue (148 g) wasdistilled under reduced pressure to yield a colourless liquid (B.p.140-142° C. @ 0.5 mmHg, 104.5 g), comprising a mixture of E and Zisomers of 3-methyl-7-phenyl-2-heptenenitrile which displays a peach,fruity, lactone, nitrile odour.

¹³C NMR data analysis: (CDCl₃, ref 77.0 ppm) 117.2/4 (CN), 95.3/9 (CH),165.4/5 (CQ), 21.0/22.8 (CH₃), 38.6 (CH₂), 26.7/27.1 (CH₂), 30.9 (CH₂),36.1/35.7 (CH₂), 142.1/2 (CQ), 128.5 (CH), 128.6 (CH), 126 (CH)

Route 2:

Reaction 4 II Plus Cyanoacetic Acid (Knoevenagel Condensation)6-Phenylhexan-2-one (II) 176.0 g, 0.10 mol Cyanoacetic acid 93.5 g, 0.11mol Piperidine 50 ml Benzene 1 ltr

Piperidine was added to 6-phenylhexan-2-one plus cyanoacetic acid inbenzene. The temperature rose from 20° C. to 35° C. and the reactionmixture temporarily solidified before turning liquid again. The reactionmixture was heated at reflux in Dean and Stark apparatus until thetheoretical amount of water had been removed.

The reaction mixture was washed twice with water (2×500 ml) and then thesolvent was removed under reduced pressure. The residue was distilled togive a mixture of III and IV (each as a mixture of E and Z isomers) as acolourless liquid (B.p. 124-128° C. @ 0.1 mmHg, 171.3 g), which displaysa peach, lactone, fruity, nitrile odour.

¹³C NMR data analysis: Compound III (CDCl₃, ref 77.0 ppm) 117.2/4 (CN),95.3/9 (CH), 165.4/5 (CQ), 21.0/22.8 (CH₃), 38.6 (CH₂), 26.7/27.1 (CH₂),30.9 (CH₂), 36.1/35.7 (CH₂), 142.1/2 (CQ), 128.5 (CH), 128.6 (CH), 126(CH) Compound IV (CDCl₃, ref 77.0 ppm) 118.0 (CN), 27.7 (CH₂), 130.0(CQ), 16.2 (CH₃), 124.5 (CH), 27.4 (CH₂), 36.0 (CH₂), 142.1 (CQ), 128.5(CH), 128.6 (CH), 125.9 (CH)

Reaction 5 Reaction of III+IV With Base Mixture of III + IV (as obtained137.9 g, 0.69 mol from distillation in reaction 4) Potassiumtert-butoxide 14.0 g, 0.13 mol Cyclohexane 500 ml

To a mixture of III/IV (as obtained from distillation in reaction 4) incyclohexane with stirring was added potassium tert-butoxide in oneportion. The temperature rose from 20° C. to 35° C. and the colourchanged from pale yellow to dark brown almost immediately. After 5minutes the reaction was washed with water (3×500 ml), dried withanhydrous magnesium sulphate, and evaporated under reduced pressure toyield a colourless product. The product was distilled to give acolourless liquid (III) (B.p. 140-142° C. @ 0.5 mmHg, 131.2 g).

¹³C NMR data analysis: (CDCl₃, ref 77.0 ppm) 117.2/4 (CN), 95.3/9 (CH),165.4/5 (CQ), 21.0/22.8 (CH₃), 38.6 (CH₂), 26.7/27.1 (CH₂), 30.9 (CH₂),36.1/35.7 (CH₂), 142.1/2 (CQ), 128.5 (CH), 128.6 (CH), 126 (CH)

GC analysis: Mixed Reaction 3 Reaction 4 Reaction 5 GC Product IsomerProduct Isomer Product Isomer Routes Ratio Ratio Ratio 3, 4 & 5 IsomerMinutes Crude % Minutes Crude % Minutes Crude % Minutes Assignment — —6.47  4 — — 6.48 Z-IV 6.64 36 6.62  6 6.63 34 6.64 Z-III — — 6.80 50 — —6.81 E-IV 6.97 57 6.95 39 6.95 63 6.98 E-III

EXAMPLE 2

A perfume in accordance with the invention was prepared by mixingtogether the following materials: % by weight Bangalol (Quest) 5 Hexylcinnamic aldehyde 12 Ionone beta 5 Iso bornyl cyclo hexanol 5 Lilyaldehyde 6 Mefrosol (Quest) 18 Methyl dihydro jasmonate super (Quest) 8Nectaryl (givaudan) 2 Peach Nitrile (Nitrile 1 and/or 2) 4 Ortholate(Quest) 24 Ethyl Safranate (Quest) 1 Galaxolide pure 10

Bangalol, Mefrosol, Methyl dihydro jasmonate super, Nectaryl, Ortholateand Ethyl Safranate are all Trade Marks.

1. A compound having the structure

where R and R¹ is each independently hydrogen or an alkyl, alkenyl,cycloalkyl or cycloalkenyl group having from 1 to 5 carbon atoms.
 2. Acompound according to claim 1, having the structure


3. A compound according to claim 1, having the structure


4. A perfume comprising one or more compounds in accordance with any oneof the preceding claims in an olfactively effective amount.
 5. A perfumeaccording to claim 4, wherein the compound is present in an amount of atleast 0.01% by weight.
 6. A perfume according to claim 5, wherein thecompound is present in an amount in the range 0.1 to 80% by weight.
 7. Aperfumed product comprising one or more compounds according to claim 1,2 or 3 or a perfume according to claim 4, 5 or
 6. 8. A method of makinga compound in accordance with claim 1, comprising i) performing an Aldolcondensation of cinnamaldehyde with a ketone; ii) hydrogenating theproduct of step i); and iii) performing a Wadsworth Emmons reaction or aKnoevenagel condensation reaction on the product step ii).
 9. A perfumecomprising 6-phenylhexan-2-one in an olfactively effective amount.
 10. Aperfumed product comprising 6-phenylhexan-2-one.
 11. A process forimparting a jasmine-type odour note to a perfume or performed product,comprising incorporating 6-phenylhexan-2-one into the perfume orperfumed product.